Blood glucose in multiparous women influences offspring birth size but not size at 2 years of age.

BACKGROUND: Gestational diabetes is associated with increased birth size. Blood glucose concentrations within the nondiabetic range affect birth size but whether this influences postnatal growth is unclear. METHODS: We measured fasting blood glucose concentrations (FBG) in 1650 singleton Caucasian pregnancies at 12 and 28 weeks' gestation and related values to birth weight and weight at 12 and 24 months of age. Pregnancies complicated by antepartum hemorrhage, gestational diabetes, preeclampsia, and prematurity were excluded. RESULTS: Mean maternal age was 30 years and 49% were primiparous. There was a weak relationship between birth weight (z score) and FBG at 12 (r = 0.1; P = .006) and 28 (r = 0.1; P < .001) weeks. FBG at 12 and 28 were correlated (r = 0.3; P < .001). Mothers at 12 and 28 weeks of pregnancy with higher FBG were shorter and heavier. The relationship between FBG at 12 and 28 weeks and birth weight was not observed in primiparous women and FBG was not associated with weight at any postnatal time point. CONCLUSIONS: These data suggest that in a low-risk United Kingdom pregnancy cohort FBG concentrations in the nondiabetic range affect birth weight in multiparous women. The effect is small (50 g change in birth weight/1 mmol/L FBG change) and does not persist into postnatal life. This implies a limited role for maternal glucose status within the normal range in determining size in infancy.

Maternal hyperinsulinism and glycaemic status in the first trimester of pregnancy are associated with the development of pregnancy-induced hypertension and gestational diabetes.

OBJECTIVE: To evaluate the relationships across a range of glucose and insulin measures at 12 weeks of gestation with the development of pregnancy-induced hypertension (PIH), gestational diabetes mellitus (GDM) and birth size. MATERIALS AND METHODS: Prospective study of pregnant women booking before 15th week of gestation. At the first antenatal visit, standard measures of height, weight, blood pressure (BP) and social status were recorded, and blood sample was drawn for measurements of fasting glucose and plasma insulin. Oral glucose tolerance test with 75  g glucose load was performed after overnight fast. Odds ratios (ORs) with 95% CI were calculated to determine the risk of developing PIH or GDM depending on quartiles of blood glucose or tertiles of plasma insulin levels. RESULTS: One thousand six hundred and fifty pregnant women were included in the study. Of them, 1484 delivered a live infant of whom 70 were preterm, 166 did not complete the study, 155 mothers developed PIH (10.4%), 18 were diagnosed with GDM (1.2%) and four had both PIH and GDM. At 12 weeks of gestation, women who became hypertensive were heavier (P<0.001), with higher BMI (P<0.001) than controls. Both systolic (P<0.001) and diastolic BPs (P<0.001) were already higher in women who developed PIH. Fasting insulin concentrations were higher in PIH group (P<0.002). Fasting glucose level >6.8 mmol/l was associated with the likelihood of delivering a macrosomic baby (OR 3.1 (95% CI: 1.21-8.0); P=0.02); the effect was heightened in multiparous mothers (OR 4.0 (95% CI: 1.4-11.1); P=0.01). Fasting plasma insulin had, however, no effect on size at birth in this study. CONCLUSIONS: Our data suggest that women who develop PIH may be metabolically challenged at early stages of pregnancy with hyperinsulinism, insulin insensitivity and slightly higher BP.

Effects of current size, postnatal growth, and birth size on blood pressure in early childhood.

OBJECTIVE: In a prospective study, we investigated the impact of early growth on blood pressure at 3 years of age. METHODS: We measured systolic blood pressure (SBP) and diastolic blood pressure (DBP) for 590 children 3 years of age and related measurements to current size and size at birth, 6 months, 1 year, and 2 years of age. RESULTS: SBP was related positively to weight at 3 and 2 years and, after adjustment for current size, negatively to weight at birth and 6 months but not at 1 or 2 years. No effect was observed for DBP. A family history of hypertension was associated with higher maternal blood pressure, greater weight, and gestational hypertension (P = .05). Mothers with a history of gestational hypertension had higher SBP and DBP values (P < .001). In multivariate linear regression analyses, SBP was influenced positively by weight at 3 years and family history of hypertension and negatively by weight at 6 months. None of the factors was associated with DBP. CONCLUSIONS: For 3-year-old children, current weight was a determinant of SBP and postnatal growth to 6 months of age was more predictive than birth weight. A family history of hypertension is important in determining maternal blood pressure. These observations suggest a window in which postnatal growth might be modified.

Gender, smoking during pregnancy and gestational age influence cord leptin concentrations in newborn infants.

BACKGROUND: Low birth weight (BW), small head circumference, reduced length, increased preterm births and neuro-endocrine dysfunctions are among known consequences of smoking during pregnancy. Few studies have linked leptin to clinical features of growth restriction associated with maternal smoking and explored interaction with other determinants of size at birth, such as gender. METHODS: Cord serum leptin concentrations were measured in 1215 term infants born to Caucasian mothers at completion of uneventful pregnancy. Serum concentrations were related to BW, gestational length, gender and maternal smoking and interaction with other determinants of size at birth evaluated. RESULTS: Smoking was more frequent in younger (P<0.001) and shorter mothers (P=0.03) from lower socio-economic groups (SEGPs) (P<0.001). Infants born to smokers were lighter (190 g less), shorter and with smaller head circumference. Cord serum leptin concentrations were higher in girls (9.8 s.d. 7.6 ng/ml) than in boys (7.05 s.d. 5.8 ng/ml) (P<0.001). Boys were heavier (BW 3.52 s.d. 0.49 kg) than girls (3.39 s.d. 0.44 kg) (P<0.001), but girls had greater skinfold thickness measurements (sub-scapular and quadriceps skinfold thicknesses 5.5 s.d. 1.6 mm and 7.6 s.d. 1.9 mm respectively; boys 5.3 s.d. 1.6 vs 7.24+/-1.90 mm, P<0.001 respectively). Multivariate analyses showed gender (P<0.001), BW SDS (P<0.001), gestational length (P<0.001) and maternal smoking (P<0.042) as factors that influenced umbilical cord serum leptin concentrations in newborns. CONCLUSION: Maternal smoking restrains foetal growth through placental vascular effects, and likely also via associated effects on leptin metabolism. More studies are needed to determine the influence that maternal smoking may have on placental syncytiotrophoblast and foetal adipose tissue.

Factors predicting ante- and postnatal growth.

Human growth is a continuous process. Studies defining factors influencing growth focus on discrete time points (e.g., birth), overlooking the conditional nature of the process. One thousand six hundred fifty Caucasian mothers who gave birth at term after an uncomplicated singleton pregnancy were studied using conditional analysis. Infant height, weight, and head circumference were obtained at birth and 6 mo of age. Data analysis, conditional upon birth size, was conducted as a stepped consideration of factors influencing phases of fetal and infant growth beginning with determinants of placental size. Placental weight was related to birth size. Seven percent of the variance in placental weight was explained by a combination of gestation at delivery, maternal size at first prenatal visit, paternal height (all positive), and increasing parity (negative). When centered on birth weight, 41% of the variance in placental weight was explained by birth weight, length of gestation, smoking during pregnancy (all positive), and a female baby (negative). Maternal and paternal stature equally influenced newborn and infant size. Conditional analysis reveals a series of modifiable (parity, length of gestation, and smoking) and nonmodifiable factors at different stages of the growth process.

The influence of cigarette smoking on antenatal growth, birth size, and the insulin-like growth factor axis.

BACKGROUND: Maternal smoking during pregnancy is associated with a reduction in birth size. Very few studies have collated changes in fetal biometry, neonatal anthropometry, biochemical factors involved in fetal growth, and measures of uterine and umbilical blood flow. METHODS: We related smoking status in 1650 low-risk, singleton Caucasian pregnancies delivering at term to measures of fetal growth, uterine and umbilical artery blood flow, placental appearance, birth size, and cord concentrations of IGF-I and -II and IGF binding protein (IGFBP)-3. RESULTS: Mothers who smoked in pregnancy were younger (P < 0.001) and shorter (P = 0.03) and from lower socioeconomic groups (P < 0.001). Mean umbilical artery blood flow at 20 wk gestation was not associated with smoking status but was significantly higher in smokers at 30 wk (P = 0.006). Uterine artery blood flow was unaffected. Smoking was associated with an increase in the percentage of abnormal placentas in a dose-dependent manner and with a 3.1-fold increased risk (odds ratio 3.1, 95% confidence interval 1.3-7.6) of abnormal umbilical artery blood flow (P = 0.009). Smoking was associated with a reduction in fetal femur length (P = 0.005) and abdominal circumference as well as birth weight, length, and head circumference but not skinfold thickness. Cord plasma concentrations of IGF-I and IGFBP-3 were lower in the babies of mothers who had smoked (P = 0.02 and P = 0.01, respectively). CONCLUSION: We concluded that maternal smoking is associated with an altered placental appearance on ultrasonography, increased umbilical artery blood flow resistance, and a reduction in longitudinal and intraabdominal organ growth. Circulating concentrations of IGF-I and IGFBP-3 along with measures of birth size but not markers of body fat are reduced, suggesting smoking results in a reduction in organ size and function.

Sexual dimorphism in the growth hormone and insulin-like growth factor axis at birth.

In rodents and humans there is a sexually dimorphic pattern of GH secretion that influences the serum concentration of IGF-I. Pattern differences can be identified in children, but it is not known how early this difference is established. We studied the plasma concentrations of IGF-I, IGF-II, IGF-binding protein-3 (BP-3), and GH in cord blood taken from the offspring of 1650 singleton Caucasian pregnancies born at term and related these values to birth weight, length, and head circumference. Pregnancies complicated by preterm delivery, antepartum hemorrhage, pregnancy-induced hypertension, preeclampsia, or gestational diabetes and where cigarette smoking continued were excluded, resulting in a cohort of 987. Cord plasma concentrations of IGF-I, IGF-II, and IGFBP-3 were influenced by factors influencing birth size: gestational age at delivery, mode of delivery, maternal height, and parity of the mother. Plasma GH concentrations were inversely related to the plasma concentrations of IGF-I and IGFBP-3; 10.2% of the variability in cord plasma IGF-I concentration and 2.7% for IGFBP-3 was explained by sex of the offspring and parity. None of the factors, apart from maternal height, influenced cord serum IGF-II concentrations (adjusted r(2) = 1%). Sex of the baby, mode of delivery, and parity influenced cord serum GH concentrations (adjusted r(2) = 2.6%). Birth weight, length, and head circumference measurements were greater in males than females (P < 0.001). Mean cord plasma concentrations of IGF-I (males, 66.4 +/- 1.2 micro g/liter; females, 74.5 +/- 1.3 micro g/liter; P < 0.001) and IGFBP-3 (males, 910 +/- 13 micro g/liter; females 978 +/- 13 micro g/liter; P < 0.001) were significantly lower in males than females. Cord plasma GH concentrations were higher in males than females (males, 30.0 +/- 1.2 mU/liter; females, 26.9 +/- 1.1 mU/liter; P = 0.05), but no difference was noted between the sexes for IGF-II (males, 508 +/- 6 micro g/liter; females, 519 +/- 6 micro g/liter; P = NS). After adjustment for gestational age, parity, and maternal height, cord plasma concentrations of IGF-I and IGFBP-3 along with sex explained 38.0% of the variability in birth weight, 25.0% in birth length, and 22.7% in head circumference. These data demonstrate that in a group of singleton Caucasian babies born at term, cord plasma IGF-I, IGFBP-3, and GH concentrations relate to birth size, with evidence for sexual dimorphism in the GH-IGF axis.

Intrauterine growth and its relationship to size and shape at birth.

Birth size and shape are commonly used as indicators of fetal growth. Epidemiologic studies have suggested a relationship between birth size and the risk of developing cardiovascular disease in later life. Certain "growth phenotypes" have been linked to the development of certain components of cardiovascular disease, particularly babies who display disproportional growth in utero. These observations are based on retrospective analysis of historical data sets. If the "Fetal Origins of Adult Disease" hypothesis is to be generalisable to the present day, then it is essential to establish whether these "growth phenotypes" exist within the normal distribution of birth size. The UCL Fetal Growth Study is a prospective study of antenatal fetal growth assessed by ultrasound at 20 and 30 wk gestation in 1650 low risk, singleton, white pregnancies. Measures of birth size were obtained and analyzed by principal components to explain shape at birth. Birth measures were also related to antenatal growth measurements to determine the strength of ultrasound evaluation in determining subsequent growth. There was significant sexual dimorphism in all measures at birth, with males heavier, longer, and leaner than females. From 20 wk of gestation onwards, males had a significantly larger head size than females. Parity, maternal height, and body mass index were important determinants of birth weight (p < 0.001). Cigarette smoking influenced birth weight, length, and head circumference (p < 0.001) but had no effect on placental size. Principal component analysis revealed that proportionality was the predominant size/shape at birth (55% of variance explained). A further 18% of variance was explained by a contrast between weight, head circumference, and length versus three skinfolds. Anthropometric measures as assessed by ultrasound at 20 and 30 wk gestation were poor predictors of birth length, weight, and head circumference (adjusted R(2) 18, 40, and 28% at 30 wk gestation scan, respectively). These predictions were not improved by including growth patterns between 20 and 30 wk. There is sexual dimorphism in a number of anthropometric measures at birth and in utero. These sex differences are important determinants of body size and shape. In a low risk population delivering at term, body shape was largely determined by proportionality between anthropometric measures. The low correlations between antenatal measures and birth size suggest that it is unwise to ascribe birth shape phenotypes to adverse events at any particular stage of gestation. The weak relationship also suggests that routine antenatal scans around 30 wk of gestation to predict growth problems are unlikely to be of benefit in the majority of cases.